P1547: CLINICAL CHARACTERISTICS OF PATIENTS WITH PROLONGED VIRAL SHEDDING OF OMICRON VARIANT IN HAEMATOLOGICAL DISEASE
Authors: Daisuke Ikeda, Kentaro Narita, Ami Fukumoto, Yuka Uesugi, Rikako Tabata, Daisuke Miura, Masami Takeuchi, Kosei Matsue
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Since the circulating severe acute respiratory syndrome coronavirus-2 variant was replaced worldwide by the Omicron variant, reduced disease severity and mortality rate of coronavirus disease 2019 (COVID-19) have been reported, even in immunocompromised populations. However, although the virus is less virulent, there is a paucity of data regarding the clinical characteristics and outcomes of prolonged Omicron infection in patients with haematologic disease (HD). Aims: To describe the longitudinal viral dynamics and clinical outcomes of Omicron breakthrough infections in patients with HD. Methods: Consecutive patients with HD at Kameda Medical Center who developed COVID-19 after the primary series of mRNA vaccination between January 2022 and January 2023 were included in this analysis for Omicron breakthrough infection. To diagnose and assess viral kinetics, reverse transcript-polymerase chain reaction (RT-PCR) for the ORF, N, and S genes was performed on nasopharyngeal specimens using the TaqPath test kit in a QuantStudio 5 Dx system (Thermo Fisher Scientific, MA, USA). The cycle threshold value (Ct) was defined as the number of cycles required to amplify the viral RNA to the detectable limit and used as a surrogate marker for estimating the viral load. As per a previous study, we defined prolonged viral shedding as Ct <30 for more than 21 days after the onset of COVID-19. Results: As of 31 January 2023, among the 1317 HD patients, 136 patients (10.3%) who developed Omicron breakthrough infection were included in this study. Approximately four-thirds of patients had received more than three doses of the vaccine. Overall, symptoms related to COVID-19 were mild, and approximately half of the patients did not require any COVID-19 treatment. Twenty-five (18.4%) patients were hospitalised, of whom 17 (68%) had received anti-CD20 antibodies within 2 years before infection. Contrary to the hospitalisation rate, death attributable to COVID-19 occurred in only four patients (2.9%). A longitudinal Ct assessment was performed in 43 patients (31.6%). Twenty-five of 43 patients (58.1%) had underlying B-cell lymphoma, and 20 (46.5%) and seven (16.3%) received anti-CD20 antibodies alone and anti-CD20 antibodies with bendamustine within 2 years, respectively. Prolonged viral shedding was observed in 14 patients (35.8%) (Figure 1). In that group, six patients (42.8%) did not achieve effective viral clearance 42 days after symptom onset, with the longest duration being 85 days. Although three patients with Ct <30 for more than 42 days developed pneumonia attributable to COVID-19, the remaining three had mild symptoms or were asymptomatic. Regarding immunological profiles, CD4+ T cells were most profoundly diminished in patients with prolonged viral shedding than in those without (median 174/μL vs. 409/μL, P <0.001). On univariate analysis, both low CD4+ (odds ratio [OR] 12.38, 95% confidence interval [95%CI] 2.99-67.21, P =0.001) and CD19+ cells (OR 6, 95%CI 1.59-26.73, P =0.011), as well as receiving anti-CD20 antibodies (OR 3.91, 95%CI 1.07-16, P =0.045) and bendamustine (OR 13.8, 95%CI 2-279.23, P =0.021) within 2 years were significant predictors of prolonged viral replication. Summary/Conclusion: Herein, prolonged Omicron viral replication was observed in approximately one-third of patients with HD, and profound CD4+ T-lymphocytopenia was a strong predictor of viral clearance failure. In the Omicron era, prolonged infection may not necessarily lead to a severe form of COVID-19; therefore, a more comprehensive study to identify risk factors is warranted.Keywords: COVID-19